Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.

Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.